Manufacturing of pharmaceutical proteins : from technology to economy / Stefan Behme.

Format:

Book

Author/Creator:

Behme., author.

Contributor:

Stefan.

Language:

English

Subjects (All):

Pharmaceutical industry.

Protein drugs.

Physical Description:

1 online resource (497 pages)

Edition:

Third edition.

Place of Publication:

Berlin, Germany : John Wiley & Sons, [2022]

Summary:

An expert, single-volume overview of the core processes and disciplines of biopharmaceutical production In the newly revised Third Edition of Manufacturing of Pharmaceutical Proteins: From Technology to Economy, renowned chemical engineer Dr. Stefan Behme delivers a comprehensive text covering all aspects of biopharmaceutical manufacturing, including legal and regulatory considerations, production facility design, quality assurance, supply chain management, emerging market regulations, and cost control. Suitable as both a reference book and a training resource, this book extensively explores the impact of digital transformation on pharmaceutical protein manufacturers and includes a brand-new chapter dedicated to digitalization. The distinguished author provides readers with practical understanding of the terminology and principles driving the various fields involved with biotechnological production, including operations, legal, finance, and IT. He also offers: * A thorough introduction to biopharmaceutical production, including value creation, product types, and biological basics * Comprehensive explorations of the technology of the manufacturing process and analytics * Practical discussions of pharmacology and drug safety, quality assurance, and pharmaceutical law * In-depth examinations of pharmaceutical protein production facilities, including facility design and the planning, construction, and commissioning of a manufacturing plant Perfect for biotechnologists working in the pharmaceutical industry, Manufacturing of Pharmaceutical Proteins: From Technology to Economy will also earn a place in the libraries of pharmaceutical engineers seeking a one-stop reference for all aspects of biopharmaceutical production.

Contents:

Cover

Title Page

Copyright

Contents

Preface to Third Edition

Preface to First Edition

List of Abbreviations

Part I Introduction

Chapter 1 Biopharmaceutical Production: Value Creation, Product Types, and Biological Basics Introduction

1.1 Role of Production in Pharmaceutical Biotechnology

1.1.1 Relationship Between Production and Development

1.1.2 Relationship Between Production and Marketing

1.2 Product Groups

1.2.1 Vaccines

1.2.2 Pharmaceuticals from Blood and Organs

1.2.3 Recombinant Therapeutic Proteins

1.2.4 Cell and Gene Therapeutics

1.2.5 Antibiotics

1.3 Basics of Biology

1.3.1 Cells and Microorganisms

1.3.1.1 Structure and Types of Cells

1.3.1.2 Metabolism

1.3.1.3 Reproduction and Aging

1.3.1.4 Viruses and Bacteriophages

1.3.1.5 Protein Biosynthesis

1.3.2 The Four Molecular Building Blocks of Biochemistry

1.3.2.1 Proteins

1.3.2.2 Nucleic Acids

1.3.2.3 Polysaccharides

1.3.2.4 Lipids

Part II Technology

Chapter 2 Manufacturing Process

2.1 Role of the Manufacturing Process in Biotechnology

2.2 Process Schematic and Evaluation

2.2.1 Drug Substance Manufacturing

2.2.2 Drug Product Manufacturing

2.2.3 Key Factors for Process Evaluation

2.3 Cell Bank

2.3.1 Expression Systems

2.3.2 Microbial Systems

2.3.2.1 Mammalian Systems

2.3.2.2 Transgenic Systems

2.3.3 Manufacturing and Storage of the Cell Bank

2.4 Fermentation

2.4.1 Basic Principles

2.4.1.1 Cell Growth and Product Expression

2.4.1.2 Comparison of Batch and Continuous Processes

2.4.1.3 Sterility and Sterile Technology

2.4.1.4 Comparison of Fermentation with Mammalian Cells and Microorganisms

2.4.2 Technologies and Equipment

2.4.2.1 Fermentation in Suspension Culture

2.4.2.2 Adherent Cell Cultures

2.4.2.3 Transgenic Systems.

2.4.3 Raw Materials and Processing Aids

2.4.3.1 Nutrient Media

2.4.3.2 Water, Gases, and Other Processing Aids

2.4.4 Overview of Fermentation

2.5 Purification

2.5.1 Basic Principles

2.5.1.1 Basic Pattern of Purification

2.5.1.2 Types of Impurities

2.5.1.3 Principles of Separation Technologies

2.5.2 Technologies for Cell Separation and Product Isolation

2.5.2.1 Cell Separation

2.5.2.2 Cell Disruption, Solubilization, and Refolding

2.5.2.3 Concentration and Stabilization

2.5.3 Technologies for Final Purification

2.5.3.1 Chromatographic Processes

2.5.3.2 Precipitation and Extraction

2.5.3.3 Sterile Filtration and Virus Removal

2.5.4 Raw Materials and Processing Aids

2.5.4.1 Gels for Chromatography

2.5.4.2 Membranes for TFF

2.5.5 Overview of Purification

2.6 Formulation and Filling

2.6.1 Basic Principles

2.6.2 Freeze‐Drying

2.7 Labeling and Packaging

Chapter 3 Analytics

3.1 Role of Analytics in Biotechnology

3.2 Product Analytics

3.2.1 Identity

3.2.2 Content

3.2.3 Purity

3.2.4 Activity

3.2.5 Appearance

3.2.6 Stability

3.2.7 Quality Criteria of Analytical Methods

3.2.8 Analytical Methods

3.2.8.1 Amino Acid Analysis

3.2.8.2 Protein Sequencing

3.2.8.3 Peptide Mapping

3.2.8.4 Protein Content

3.2.8.5 Electrophoresis

3.2.8.6 Western Blot

3.2.8.7 HCP Enzyme‐Linked Immunosorbent Assay (ELISA)

3.2.8.8 Analytical Chromatography

3.2.8.9 Infrared (IR) Spectroscopy

3.2.8.10 UV/Vis Spectroscopy

3.2.8.11 Mass Spectrometry

3.2.8.12 Glycoanalytics

3.2.8.13 PCR

3.2.8.14 DNA/RNA Sequencing

3.2.8.15 Endotoxins and Pyrogen Testing

3.2.8.16 Bioburden Test

3.2.8.17 Virus Testing

3.2.8.18 TEM

3.2.8.19 Circular Dichroism

3.2.8.20 Differential Scanning Calorimetry

3.3 Process Analytics

3.3.1 Fermentation.

3.3.2 Purification

3.3.3 Formulation and Packaging

3.4 Environmental Monitoring

3.5 Raw Material Testing

3.6 Product Comparability

Part III Pharmacy

Chapter 4 Pharmacology and Drug Safety

4.1 Action of Drugs in Humans

4.1.1 Pharmacokinetics

4.1.2 Pharmacodynamics

4.1.2.1 Principles of Phenomenological Effects

4.1.2.2 Parameters of Drug Effects

4.2 Routes and Forms of Administration

4.3 Drug Study

4.3.1 Pre‐Clinical Study

4.3.2 Clinical Study

4.3.2.1 Phases of Clinical Studies

4.3.2.2 Design and Conduct of Clinical Trials

4.4 Path of the Drug from the Manufacturer to Patients

4.5 Drug Safety

4.5.1 Causes and Classification of Side Effects

4.5.2 Methods for Supervising Drug Safety (Pharmacovigilance)

4.5.3 Measures upon Incidence of Adverse Reactions

Part IV Quality Assurance

Chapter 5 Fundamentals of Quality Assurance

5.1 Basic Principles

5.2 Benefit of Quality Assurance Activities

5.3 Quality Management According to ISO 9000

5.3.1 Fields of Activity

5.4 Structure of Quality Management Systems

5.5 Quality Management System Components in the Pharmaceutical Area

5.5.1 Documentation

5.5.2 Failure Prevention and Correction

5.5.3 Responsibility of Management and Training of Personnel

5.5.4 Audits

5.5.5 External Suppliers

5.5.6 Contract Review

5.6 Quality Assurance in Development

Chapter 6 Quality Assurance in Manufacturing

6.1 GMP

6.1.1 Personnel

6.1.2 Premises and Equipment

6.1.2.1 Measures to Avoid External Contamination

6.1.2.2 Measures to Avoid Cross‐Contamination and Product Confusion

6.1.3 Equipment Qualification

6.1.4 Process Validation

6.1.5 Computer Validation

6.1.6 Documentation

6.2 Operative Workflows under GMP Conditions

6.2.1 Product Release and Deviation Management.

6.2.2 Changes in the Manufacturing Process

6.3 Production of Investigational Drugs

A Case Study Part IV: Warning Letters by FDA

Part V Pharmaceutical Law

Chapter 7 Pharmaceutical Law and Regulatory Authorities

7.1 Fields of Pharmaceutical Law

7.2 Bindingness of Regulations

7.3 Authorities, Institutions, and Their Regulations

7.3.1 FDA

7.3.2 EMA

7.3.3 German Authorities

7.3.4 Japanese Authorities

7.3.5 Authorities of Growth Markets

7.3.5.1 China: National Medical Products Administration (NMPA)

7.3.5.2 Brazilian Agência Nacional de Vigilância Sanitária (National Health Surveillance Agency, ANVISA)

7.3.6 Other Important Institutions

7.3.6.1 US Pharmacopoeia

7.3.6.2 ICH

7.3.6.3 ISO

7.3.6.4 WHO

7.3.6.5 PIC/S

7.3.6.6 ISPE

7.3.6.7 PDA

7.4 Official Enforcement of Regulations

7.5 Drug Approval

B Case Study Part V: Clinical Trials for Protein Products

B.1 Mabthera®/Rituxan®

B.2 Enbrel®

B.2.1 Adult Patients with Rheumatoid Arthritis

B.3 Remicade® Infliximab

B.3.1 Adult Rheumatoid Arthritis

B.4 Humira® 40 mg

B.5 Lucentis®

B.5.1 Treatment of Wet AMD

B.6 Zaltrap®

Part VI Production Facilities

Chapter 8 Facility Design

8.1 Basic Principles

8.2 GMP‐Compliant Plant Design

8.2.1 Production Flow Diagram

8.2.2 Conceptual Plant Layout

8.2.2.1 Is the Facility Fit for the Intended Purpose?

8.2.2.2 Is the Facility cGMP Compliant?

8.2.2.3 Is the Facility Flexible?

8.2.2.4 Can the Facility Be Expanded?

8.2.2.5 Is It Possible to Separate the Core Process from the Support Functions?

8.2.2.6 Is the Plant Capacity Optimized and Are Synergies with Existing Facilities Used?

8.2.3 GMP Flow Analysis

8.2.4 Zoning Concept

8.3 Basic Concepts for Production Plants

8.3.1 Single‐ and Multiproduct Plants.

8.3.2 Fractal and Integrated Configuration

8.3.3 Flexible and Fixed Piping

8.3.4 Steel Tanks and Disposable Equipment

8.4 Clean and Plant Utilities

8.4.1 Clean Utilities

8.4.1.1 Water

8.4.1.2 Clean Steam

8.4.1.3 Gases and Process Air

8.4.2 Plant Utilities

8.4.3 Waste Management

8.5 Equipment Cleaning

8.6 Clean Rooms

8.6.1 Separation of Zones by Clean Room Design

8.6.2 Finishing of Floors, Walls, and Ceilings

8.6.3 HVAC Installations

8.6.4 Qualification

8.7 Automation

8.8 QC Laboratories

8.9 Location Factors

8.9.1 Cost

8.9.2 Personnel

8.9.3 Permitting

8.9.4 Synergies with Existing Facilities or Units

8.9.5 Logistics

8.9.6 Know‐How and Intellectual Property Protection

8.9.7 Other Risks

8.9.8 Market Access

8.9.9 Language and Culture

Chapter 9 Planning, Construction, and Commissioning of a Manufacturing Plant

9.1 Steps of the Engineering Project

9.1.1 Planning

9.1.2 Construction

9.1.3 Commissioning, Qualification, Validation

9.2 Project Schedules

9.3 Cost Estimates

9.4 Organization of an Engineering Project

9.4.1 Expert Groups Involved

9.4.2 Role and Selection of Contractors

9.4.3 Contracts and Scope Changes

9.5 Successful Execution of an Engineering Project

9.6 Legal Aspects of Facility Engineering

9.6.1 Health, Safety, and Environmental Law

9.6.2 Building Law

Part VII Economy

Chapter 10 Production Costs

10.1 Drug Life Cycle

10.2 Position of the Manufacturing Costs in the Overall Cost Framework

10.3 Basic Principles of Cost Calculation

10.3.1 Nominal Accounting - Actual Accounting

10.3.2 Cost Accounting - Profit and Loss Accounting

10.3.3 Direct Costs - Indirect Costs

10.3.4 Fixed Costs - Variable Costs

10.3.5 Relevant and Irrelevant Costs

10.3.6 Cost Type, Cost Center, and Cost Unit.

10.4 Costs of Biotechnological Manufacturing Processes.

Notes:

Includes bibliographical references and index.

Description based on print version record.

Other Format:

Print version: Behme, Stefan Manufacturing of Pharmaceutical Proteins

ISBN:

9783527833801

3527833803

9783527833818

3527833811

9783527833795

352783379X

OCLC:

1289932184